In this proposal the role of serotonin (5-HT) in the descending control of spinal nociceptive neurons will be examined. The iontophoretic intracellular horseradish peroxidase (HRP) and immunocytochemical techniques will be combined in order to simultaneously determine several characteristics of a single neuron. The cell's morphology, peripheral and descending physiological input, presence and distribution of 5-HT immunoreactive axonal contacts and responses to iontophoretically applied 5-HT will be examined in an attempt to answer three specific questions: 1) Does 5-HT, applied by iontophoresis, mimic the effects of nucleus raphe magnus (NRM) stimulation on physiologically characterized and morphologically identified cat lumbar laminae I and II neurons? 2) Does the 5-HT action correlate with the distribution of 5-HT immunoreactive axonal contacts on these same neurons? 3) Does methysergide, also applied by iontophoresis, antagonize the action of 5-HT and the effects of NRM stimulation on these neurons in a similar manner and to a similar degree? The simultaneous determination of several neuronal characteristics allows one to address complex issues of neural circuitry which are fundamentally important to all aspects of the nervous system. This proposal should provide new information about the anatomy, physiology and pharmacology of a major neural circuit involved in nociception -- the integration and processing of information at the level of the superficial dorsal horn of the lumbar spinal cord. Such information should prove useful in better understanding the basic processes of nociception, leading to significant advances in pain management.